Effects of methylene blue on rhythmic activity and membrane potential in the canine proximal colon

The hypothesis that methylene blue has a direct effect on colonic muscle cells was tested. Intracellular recordings were made from cross-sectional preparations of canine proximal colon. Cells through the circular layer were impaled and membrane potentials ranging from -81 mV at the submucosal surface to -46 mV at the myenteric border were recorded. Methylene blue (10(-5) M) depolarized cells near the submucosal border by an average of 43 mV and slow-wave activity ceased. The loss of slow-wave activity could be explained by the depolarizing effects of methylene blue rather than a specific effect of methylene blue on the pacemaker mechanism. Other experiments suggested that the depolarizing effects of methylene blue were not confined to muscle cells within the submucosal pacemaker region. Depolarization of cells was noted throughout the circular layer, but the magnitude of the depolarization decreased with distance from the submucosal border. After methylene blue, the gradient in resting potential across the circular layer was greatly reduced or abolished. The data suggest that methylene blue is not necessarily a specific probe for interstitial cells and has direct effects on smooth muscle cells in the canine proximal colon. This effect is similar to treatments that are known to block the electrogenic sodium pump.